Mass cytometry is a newly developed technique for studying biological samples. The technique was originally developed to study cell populations in which samples of interest containing various biological cells were “stained” with affinity probes such as antibodies that are attached to elemental tags. The amount of affinity probes of a given type attached to each cell can be used to characterize each individual cell. The amount of affinity probe of each type is directly related to the amount of the associated elemental tag. The amount of the elemental tagging material can be measured by passing the cell through an inductively coupled plasma (ICP) ion source of a mass cytometer. The technique of “staining” biological material with affinity probes with elemental tags has recently been extended to the field of imaging of biological tissue. In imaging mass cytometry, a tissue of interest is “stained” with affinity probes/molecular tags and laser ablation can be used to extract the elemental tags from discrete locations (pixels) on the tissue. Imaging mass spectrometry follows a similar method, except that it relies on the detection of atoms naturally present in the sample rather than the labelling atoms in the elemental tags.
A limitation of mass cytometry is the efficiency of introducing biological samples such as cells into the mass cytometer. Cell introduction efficiency of commercial mass cytometers is about 30%. This means that more than two-thirds of biological cells in a sample are lost before they can be recorded by the mass cytometer.
A further limitation of laser-ablation based imaging mass cytometry and laser-ablation based imaging mass spectrometry is the low pixel recording rate. The pixel recording rate is limited by the washout time of the laser ablation cell and the connecting gas conduits. Even the fastest laser ablation cells have a washout time on the order of 30 ms. This is much slower than the intrinsic recording capabilities of the mass cytometer or mass spectrometer. In a typical mass cytometer cell throughput can be as high as 1000 cells per second; however, the spread of the laser ablation plume as it travels through the laser ablation apparatus, i.e. washout time, limits the pixel rate to about 30 pixels per second. Moreover, in the process of laser ablation each pixel of material is vaporized and converted into an aerosol. The aerosol plume is then transported to the ICP source via a gas conduit. One of the problems with this approach is that a fraction of the aerosol plume can contaminate neighboring areas, e.g., neighboring pixels, of the tissue sample. Some fraction of the aerosol plume can also be lost during transport through the gas conduit connecting the laser ablation chamber to the ICP ion source. In addition, the gas dynamic spreading of the aerosol plume during transport to the ICP source further limits the washout time. Therefore, in view of these constraints, it is desirable to avoid remote ablation method and aerosol plume formation of a biological sample and thereby improve the throughput of imaging mass cytometry and imaging mass spectrometry.